Early-Onset Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes With 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin

Abstract

PURPOSE Early-onset (EO) colorectal cancer (CRC, age < 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years). MATERIALS AND METHODS Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non–cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered. RESULTS Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P < .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P = .97), higher N2 disease rate (24% v 22%, P < .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P < .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value < .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value < .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value = .85). CONCLUSION Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.

Insights From the IDEA Collaboration: Are They Enough?

“…Simultaneously, efforts must be put into understanding the biology of this heterogenous disease entity and determine how best to treat these patients to improve cancer outcomes. Large trial populations such as those reported by Fontana et al 1 would ideally collect greater details of patient characteristics and comorbidities to help this understanding. Given the increasing incidence since the IDEA collaboration studies, we also need to explore changes that may have occurred over time to understand the increasing incidence.…”

“…Fontana et al 1 have recently reported in the Journal of Clinical Oncology on the IDEA database. Historically, more than 90% of colorectal cancer (CRC) diagnosis occurred in patients > 50 years (late-onset CRC [LO-CRC]).…”

“…Current observations paint the picture of a disease with aggressive biology; however, these data are limited to retrospective reports. 6,7 Fontana et al 1 reported individual patient data from 16,349 patients with stage II or III CRC in the IDEA database and compared EO-CRC with LO-CRC regarding population characteristics, adjuvant treatment adherence, toxicity, and outcomes. 8 This represents the first published study using prospectively collected trial data to differentiate between age groups exploring tolerance and survival outcomes.…”

Reply to A. Smith et al

“…We thank Smith et al 1 for their correspondence in relation to our article. 2 The increased incidence in early-onset colorectal cancer (EO-CRC) was noticed since the beginning of the 90s in the United States, possibly highlighted by the accelerated opposite trends in adults older than 50 years as an effect of screening programs. 3 Importantly, this phenomenon has been observed with different magnitudes in different countries; this suggests that this is unlikely due only to screening programs masking a possible global increase, but more likely to different early-life cancerogenic exposure.…”

“…The studies included in the IDEA database recruited patients from 2007 to 2017, thus during a relevant and contemporary timeframe, although limited. 2 In Figure 1, we present, to our knowledge, for the first time the accrual curve including the percentage of patients with EO-CRC by year. In view of different recruitment rates in each trial at different time points, changes in incidence are challenging to appreciate.…”